Velocardiofacial syndrome (VCFS), caused by a microdeletion on chromosome 22q1 1.2, is associated with multiple congenital anomalies, neurocognitive deficits, and a neuropsychiatric phenotype duringchildhood that affects up to 65 percent of patients, and includes ADHD, oppositional defiant disorder and anxiety. Although up to 30 percent of adults with this syndrome develop schizophrenia (SZ) or bipolar disorder (BPD), currently we do not understand the relation between childhood psychiatric disorders in VCFS and the deterioration in adaptive/psychosocial functioning or mood regulation that may signal the eventual onset of SZ or BPD in late adolescence or early adulthood. We hypothesize that a subset of VCFS-affected subjects with child psychiatric disorders will demonstrate deficits on markers of biological vulnerability (i.e., neuroanatomic anomalies, and impairments in eye tracking, sustained attention and memory) that have been associated with SZ and/or BPD in the general population. We predict that this subset of children and youth will demonstrate, during a three year period, a deterioration in adaptive/psychosocial function or mood regulation that may signal the eventual onset of SZ or BPD in adulthood. We anticipate that this project will provide the first phase of data for a clinically based longitudinal study in which children with VCFS will be followed into adulthood to determine the eventual psychiatric outcome of each patient. Accordingly, the aims described in this application are designed 1) to increase our understanding of the natural history of child psychiatric disorders in VCFS; 2) to assess whether putative biomarkers for psychosis emerge and co-occur in a subset of psychiatrically-disordered children with VCFS; and 3) to explore the extent to which the presence of biomarkers in VCFS-affected children contribute to deterioration in adaptive/psychosocial functioning or mood regulation over time. To address these aims, children and youth will be assessed across multiple domains, including neuropsychological function, sustained attention, eye-tracking performance, brain morphology and clinical symptomatology.